Day 1: 0.05 mL/kg, no reaction Day 4: 0.1 mL/kg, no reaction Day 27: 0.12 mL/kg, immediately followed by vomiting, defecation, leg tremors, loss of consciousness and death in 1/2 h. By 1907, Richet had determined that 1 ‘the anaphylactogenic property resided in serum taken from inoculated dogs and 2 after recovery from anaphylactic reactions, the dogs had become immune to the previous injurious dose of causative agent’ 1. Richet was awarded the Nobel Prize in Medicine or Physiology in 1913. Portier was not included. Two subsequent major milestones from the allergy and immunology perspective that followed over time included the description of passive transfer of reaginic antibody by Prausznitz and Kustner in 1921 and the laboratory demonstration of “reagin” as the 5th isotype antibody, IgE, described by the Ishizakas in 1968. Another important finding is from the physiologic perspective, and indeed, both Richet and Portier had positions in separate physiology laboratories before their collaboration. The measurements from 8 patients who had indwelling catheters and monitoring equipment, who experienced anaphylactic reactions during cardiac surgery, show not only drops in systemic vascular resistance by 50% but in 2 patients, elevations in pulmonary artery pressures, even without bronchoconstriction in 1 patient 3. Cardiac output and stroke volumes both increased 3. The potentially catastrophic distributive shock from anaphylaxis can be associated with surges in pulmonary arterial pressures, which creates a challenging and unanticipated medical emergency for anaesthesia physicians and mid-level professionals and a threat to life for the patient and their families and friends. The immediate onset of signs of anaphylaxis and then death within ½ hour after a parenteral injection of antigen that the dog, Neptune, experienced in an investigation is analogous to the finding that there may be no cutaneous findings such as hives or angioedema of the face, lips or tongue or symptoms of pruritus in people experiencing fatal anaphylactic reactions 4. In a study of 25 unselected cases in the Office of the Medical Examiner in Chicago, Illinois from 1989 to 2001, wherein the mean age of the deceased persons was 59 years of age (range 17–91 years), the onset of anaphylaxis was within 30 min of exposure in 21/25 cases, and death occurred within 60 min in 13/25 cases 4. Flushing or generalized pruritus was identified in 3/25 cases and only 1 case had presence of urticaria 4. Twelve reactions occurred in a private residence and 7 reactions were in inpatient medical or long-term care facilities 4. Post-mortem serum tryptase concentrations were elevated in 4/7 cases (from 78 to 200 ng/mL), and self-administered adrenaline (epinephrine) was utilized in just 1 of 5 patients, which is similar to other reports 5. In this issue, there are important reports 6-8 regarding fatal anaphylactic reactions. McKenzie et al. explored findings from 371 fatalities from anaphylaxis in coroner cases from Australia with data from 2003 to 2022 6. As has been described previously, some 90.7% of patients who died from fatal food anaphylaxis had a diagnosis of asthma 6. In contrast, but of note, asthma was a working diagnosis in 22.6% of patients who died from fatal reactions to radiocontrast media and 21% of patients who succumbed from insect stings 6. Coveney et al. explored pre-hospital care from 2016 to 2023 of primarily fatal food anaphylaxis from the National Child Mortality Database on asthma and anaphylaxis in England 7. In this population, the estimated onset of symptoms to cardiac arrest was 14 min, and 74% of the deceased patients had received either no adrenaline or 1 dose 7. Coveney et al. also explored whether pathophysiology of the deaths was from the upper airway (stridor, massive swelling, etc.), lower airways, or cardiovascular (faintness, collapse, etc) causes 8. Nearly all cases of fatalities from foods were either from the upper or lower airways as opposed to cardiovascular collapse 8. It is my belief that as much as we know, there continues the urgent need to focus on how to prevent deaths, near miss episodes and even milder cases of anaphylaxis as well as to reduce the number of patients or care givers who have to decide whether to self-administer adrenaline and aren't confident of what to do or whether to go to an emergency department and face delays because of overcrowded facilities. While there are differences of professional opinion and potential policy decisions regarding whether emergency-use adrenaline might be made available in public spaces or even made available without prescription, others have discussed inconsistencies in recommendations whether to advise self-administered adrenaline for food and venom allergic patients with 5% or less risks of anaphylaxis 9. In resource insufficient areas, where auto-injectors or intranasal adrenaline are not available, physicians and health care professionals may resort to ordering vials of adrenaline (1:1000) and teaching how to aspirate with a syringe and then inject in preparation for an emergency. All of us should verify that our patients or appropriate care givers can demonstrate how to inject or administer adrenaline in anticipation of an anaphylactic reaction and not solely take an H1 antihistamine or 2–4 dosages of such as first line management. I support the argument that health care policy makers and systems should pay for sufficient time for teaching in the office or emergency department regarding the diagnosis and treatment of anaphylaxis including food allergies. We need to make sure that we ourselves and our staff are up-to-date on professional society recommendations, policies of regulatory agencies, and routes of and devices to administer adrenaline. Just as we recognize the pioneering work of Richet and Portier and ‘funding and resources’ provided by the Prince Albert I of Monaco from 125 years ago, it is imperative to continue investigative efforts and collaborative partnerships to achieve tolerance and lasting remissions as opposed to desensitisations and reduced risks of anaphylaxis for our patients. And we need to continue to educate in a constructive way patients and others about the association of fatalities from foods during anaphylaxis in people with asthma and that older patients experiencing anaphylaxis are likely to have co-morbid cardiovascular conditions 4. Paul Greenberger conceived and prepared the manuscript and reviewed the literature. Paul Greenberger is a consultant for Allergy Therapeutics.
PA Greenberger (Mon,) studied this question.